Inlet device and its use

ABSTRACT

An inlet device for a reactor vessel ( 5 ) intended for a separation method comprising retaining a substance on a separation medium from a liquid passing through the reactor vessel ( 5 ) which contains the separation medium. The device comprises (a) a distributor block ( 7 ) enabling a liquid flow to pass through the block into the reactor vessel ( 5 ), (b) an inlet block ( 3 ), (c) a distribution chamber ( 1 ) defined by a space between the distributor block ( 7 ) and the outlet side ( 11 ) of the inlet block ( 3 ), (d) at least one conduit (I;  13   a,   13   b  . . . ) passing through the inlet block ( 3 ) from the inlet side ( 10 ) to the outlet side ( 11 ) of said inlet block ( 3 ) and ending in the distribution chamber ( 1 ), said at least one conduit being able to distribute liquid into the distribution chamber ( 1 ), (e) a gross liquid flow direction going perpendicular to the plane of the interface between the distribution block ( 7 ) and the distribution chamber ( 1 ). One characteristic feature is that one or more of said at least one conduits ( 13   a,   13   b  . . . ) in the chamber ( 1 ) are capable of moving selectively the liquid next to the inlet side surface ( 11 ) of the distribution chamber ( 1 ) along and/or against said surface ( 11 ).

TECHNICAL FIELD AND BACK-GROUND PUBLICATIONS

The present invention relates to a device to be used at the inlet end ofa reactor vessel in which one or more substances are retained on aseparation medium from a liquid passing through the vessel. This kind ofseparation can be carried out in batch-wise mode or in chromatographymode. The separation medium is typically in form of porous or non-porousparticles that may be present as a packed or fluidised bed, the latterencompassing fully disordered fluidised beds (batch-wise mode) orclassified or stabilised fluidised beds (chromatography fluidised mode).

The “term retained on a separation medium” means that the substance(s)are capable of interacting with the separation medium, such as inseparations based on (a) affinity adsorption including ion exchange andother kinds of non-covalent bindings, (b) covalent binding and/or (c) onsize exclusion.

Various devices to be used at the inlet side of this kind of reactorshave been described in the background art. See for instance WO 9218237(Amersham Pharmacia Biotech AB) and WO 0025883 (application noPCT/SE99/01957, Amersham Pharmacia Biotech AB), both of which areincorporated by reference.

Typically inlet devices have comprised

(a) distributor means which comprises a block or a plate and permits aliquid flow to pass through into the interior of the reactor vessel,

(b) an inlet block or plate having one or more through-going conduitspermitting liquid to pass through the inlet block or plate,

(c) a distribution chamber defined by a space between the distributormeans and the inlet block or plate, and

(d) a gross flow direction passing from the distributor chamber to andthrough the reactor vessel.

A recess in the inlet block typically defines the distribution chamber.The distribution block covers the recess. If the recess is tapered theremay be no distinct walls of the chamber. If chamber has walls they arein the context of the invention included in the outlet side of the inletblock or plate, if not otherwise specified.

There has been a recent suggestion in the field to equip the outlet ofthe inlet conduits in the inlet block with “sprinkler means” (nozzles)(WO 0025883, FIG. 4, pages 16-17). The main purpose of the design hasbeen to facilitate an even distribution of liquid to the distributorblock. There is a suggestion that this design possibly will assist inkeeping the chamber clean from sticky components.

The design with sprinkler means is illustrated in FIG. 1 of the presentspecification. There is a distribution chamber (1) having one or moreconduits (2 a,2 b . . . ) projecting and permitting liquid flow throughan inlet block (3) into the chamber (1). The chamber (1) is viadistribution means (4) in liquid communication with the interior (5 a)of a reactor vessel (5 b) in which a separation medium is present. Thedistributor means may comprise a net/mesh (6) and/or a block(distributor block, 7) having open through passing channels permittingliquid flow between the chamber (1) and the interior of the reactorvessel (5). On the chamber end of each incoming conduit (2 a,2 b . . . )there are sprinkler means (nozzles) (8) in form of a cap and openings(9) placed circularly in the wall of the end of the conduit just beforethe cap. The conduits (2 a,2 b . . . ) extend from the inlet block (3)from the inlet side (10) to the outlet side (11) (=inlet side/surface ofthe distribution chamber). The incoming liquid is in the variant showndistributed radially in a plane perpendicular to the flow direction inthe conduit concerned, i.e. perpendicular to the central axis (12) ofthe chamber.

To each of the conduits (2 a,2 b . . . ) there are connected a tubing(31 a,31 b) that comes from a common tubing (37) equipped with a pump(38). Between the outlet end (11) and the nozzle (8) the conduit has acentral tubular part in form of a central channel (32). At the outletend of the reactor vessel (5) there is an outlet tubing (35) and anoutlet adapter comprising a collector block (33), a collector chamber(34), an end block (36) with an outlet opening (39).

The inlet devices discussed above may be present as a bottom adapter oras a top adapter if the flow through the reactor vessel is upward ordownward, respectively. If the flow direction is upward the outlet side(11) becomes the bottom/bottom surface of the distribution chamber.

The outlet side (11) is typically also the inlet side of thedistribution chamber (1).

For reasons of simplicity the term “block” in the instant specificationcontemplates true block dimensions and plate dimensions, if nototherwise specified.

In WO 91 00799 (Upfront Chromatography) there is described certain inletdevices that create a turbulent zone at the inlet end of the reactorvessel and a non-turbulent zone remote from the inlet end. The length ofthe turbulent zone is dependent on the flow velocity. The turbulent zoneis created by the presence of agitating means (for instance a stirrer)in the inlet end of the reactor vessel. In many of the variantsdescribed in this publication the use of a distributor block becomesredundant. Liquids may enter through a side-wall of the reactorvessel/distributor.

Problems Associated with Back-ground Techniques

The liquid containing the substance to be adsorbed often containsparticulate matters that have a tendency to sediment due toinappropriate flow conditions in various parts of a separation system,such as in inlet devices. Once sedimented, particulate material maystart adhering to surfaces due to an inherent stickiness. This isparticularly true for biologically derived liquids containing forinstance cells, cell debris and/or other sticky particulates and/orsticky solutes. This problem has been found to be most severe forliquids deriving from cell culture broths and/or containing mammaliancells and/or mammalian cell debris. In inlet devices, for instanceaccording to WO 0025883, it has turned out that particles of theseparation media may assemble in the distribution chamber even if thereis a check valve in the distributor block. Consequently the inletdevices described above are in need to be improved. The presentinvention has as its major objective to provide solutions to this kindof problems.

OBJECTIVES OF THE INVENTION

Accordingly a first objective of the invention is to provide an improvedinlet device that at least partially circumvent the problems justdiscussed.

A second alternative is to provide an improved method in which theseproblems are reduced.

A third objective is a method for reducing the same problems.

DRAWINGS

FIG. 1 represents a cross-sectional view of the closest prior art as itis described in WO 0025883 (FIG. 4, pages 16-17).

FIGS. 2a-f are cross-sectional views of conduits Ia and Ib with twokinds of nozzle functions(FIGS. 2a-c and FIGS. 2d-f, respectively). Theviews are along the planes indicated (A, B and C).

FIG. 3 shows schematically a central vertical cross-sectional view of adistributor block, which has been used with the conduit arrangementsshown in FIGS. 2a-f. See further WO 0025883.

FIGS. 4a-e illustrate variants of arrangements of conduits in thedistribution chamber with the directions of the openings in the conduitsindicated. The view is from above and perpendicular to the central axisof the inlet surface of the distribution chamber. The outlet surface(11) of the inlet block (3) is circular. The various arrangements havebeen challenged with liquids containing biomasses.

The same numerals have been used for parts that have the same function.

The Invention

The first aspect of the invention an inlet device for a reactor vesselintended for the kind of separations defined in the introductory part.Our new devices are based on the previously known variant defined inFIG. 1 and comprises:

(a) a distributor block (7) enabling a liquid flow to pass through theblock into the reactor vessel (5),

(b) an inlet block (3),

(c) a distribution chamber (1) defined by a space between thedistributor block (7) and the outlet side (11) of the inlet block (3),

(b) at least one conduit (I; 13 a,13 b . . . ) passing through the inletblock (3) from the inlet side to the outlet side (11) of the inlet block(3) and ending into the distribution chamber (1), said at least oneconduit being able to direct liquid flow into the distribution chamber(1),

(e) a gross liquid flow direction going perpendicular to the plane ofthe interface between the distribution block (7) and the distributionchamber (1), i.e. in principle the same flow direction as in the reactorvessel (5).

The present inventors have recognized that the problems discussed abovecan be at least partially overcome for this kind of devices byincreasing selectively the liquid movement next to and along the inletside surface (11) of the distribution chamber (1). In other words theliquid from one or more up to all of the conduits I should be directedagainst and/or parallel with the inlet side surface (11) of thedistribution chamber (1). This can be accomplished by arranging theincoming liquid from said at least one conduit to give a liquid movementat the inlet side surface (11) of the distribution chamber (1), whichmovement comprises

(a) one first component (component 1) that has a circular direction in aplane perpendicular to and around the central axis (12) of the inletsurface (11) of the distribution chamber (1),

(b) one second component (component 2) that has a direction that isperpendicular to said plane and against the gross flow direction.

Component 1 is thus tangential relative to the centre of surface (11).In this context the inlet surface (11) of the distribution chamber (1)should be circular or in form of an essentially regular polygon,preferably having corner angles >90° such as >100°. See below.

A preferred feature of this aspect is that

A. one or more conduits (Ia; 13′a,13′b . . . ) of said at least oneconduit (I;13 a,13 b . . . ) are capable of directing liquid radially inone or more distinct directions, all of which distinct directions are

(i) within an interval of 0°-180°, such as 0°-145° or 0°-90°, around thecentral axis of the conduit, i.e. the angle between two distinctdirections is >0° and <180°, and for the smaller intervals >0° and <145°or >0° and <90°, and/or

(ii) in an interval of 90°-180° relative to the liquid flow along thecentral axis of the conduit, i.e. ally or partially opposite the liquidflow along the central axis, and

B. said one or more conduits (Ia; 13′a,13′b . . . ) are mounted in theoutlet side (11) of the inlet block (3) in a manner enabling a circularliquid movement around the central axis (12) and along the inlet side(11) of the distribution chamber (1), and/or a liquid movement directedtowards the same side (11).

See FIGS. 2a-c and 4 a-e.

The term “distinct direction” means that the flow is coming from one ormore openings pointing in the same direction of one and the sameconduit. Se for instance FIGS. 2a-f. The number of conduits la(13′a,13′b . . . ) in a distribution chamber (1) is preferably 2, 3, 4,5, 6 and up to 25. The number of distinct flow directions for eachconduit Ia may be 1, 2, 3, 4, 5, 6 and up to 10 or even more.

In addition to the conduits (Ia; 13′a,13′b . . . ), the conduits I mayalso comprise one or more conduits (Ib; 13″a, 13″b . . . ), each ofwhich direct liquid flow in at least two essentially opposite directionsfrom the central axis of the conduit, ire. at least two flow directionsat an angle ≧180° relative to each other, for instance 180°±45°, such as180°±10°. In preferred variants, this kind of conduits may have 2, 3, 4,5, 6 and up to 20 distinct directions which may be regularly and/oressentially evenly distributed around the central axis of the conduit.The liquid flow from this kind of conduits may also be directedaccording to (ii) above, e.g. fully or partially against the flowpassing along the length axis of the conduit. The number of conduit Ibin the distribution chamber (1) may be 1, 2, 3, 4, 5, 6 and up 10 oreven more.

See FIGS. 2d-f and 4 a-e.

One or more up to all of the conduits Ia and Ib may be slidably mountedin the inlet block (3). By this is meant that the conduits are rotatablealong their length axis and/or adjustable in a length-wise manner, i.e.into or out of the distribution chamber (1) through the inlet side (11)of distribution chamber (1). There are also other alternatives forarranging for the conduits to be movable within the distribution chamber(1).

One or more up to all of the conduits Ia and Ib may be fixedly mountedin the inlet block (3).

If there are movable conduits, it may be arranged so that one or more upto all of them are controlled from an outside position as to heightabove the bottom surface (11), degrees of rotation and opening andclosing. This control may be performed manually or automaticallyaccording to preset values depending on the incoming liquid fluid asdiscussed below. Manual operation is simplest to forecast because theconduits may be slidably mounted in the holes in the inlet block (3).Closing/opening may be performed by attaching and removing clamps or byways of valves on tubings leading to each conduit (not shown).

The conduits may be of the same or different outer diameter. By usingconduits of the same outer diameter conduits of different functionalkinds thus become easily interchangeable.

A certain kind of conduit is a so-called “dummy conduit” which isnon-functional with respect to letting flow through. Dummy conduits mayreplace functional conduits if they are of the same outer diameter.

In the most preferred and simple variants of the invention at thepriority date, the reactor vessel is placed vertically with the inletdevice at the lower part of the vessel, i.e. the gross liquid flowdirection through the inlet device (3) and the reaction vessel (5) isupward. This is in analogy with FIG. 1.

Geometric Configuration and other Features of the Various Parts of theInlet Device

Cross-sectional surfaces/areas discussed in this text are alwaysperpendicular to the gross liquid flow direction.

The Interface

(a) between the inlet block (3) and the distribution chamber (1) (areaI),

(b) between the distribution chamber (1) and the distribution block (7)(area II) and

(c) between the distributor block (7) and the reactor vessel (5) may beof different geometric forms as described in WO 0025883, for instance.For interface (a) (inlet side (11) of the distribution chamber (1)), thepreference is for a regular pentagon, hexagon etc, the general rulebeing that corner angle should be as close as possible to 180°. In otherwords rounded forms (such as circular) are preferred because they willgive a minimum in dead-volumes where particulate materials can assemble.The sizes of the areas may be the same or different, with preference forarea I≦area II≦area III. Area I and area II may be connected bydistinguishable walls of the distribution chamber (1) that are more orless parallel to the gross flow direction. This is analogy with FIG. 1.The chamber (1) may also be tapered or rounded along the direction ofthe central axis (12) making walls more or less indistinguishable.

The distributor block (7) may be as described in the background art(FIG. 1), i.e. a perforated plate (7), possibly combined with a net (6)or possibly a net (6) alone. In an alternative (FIG. 3) it may be a trueblock (14) in which there are channels (15), possibly containing a checkvalve (16) for rendering it difficult for particles of separation mediato enter the distribution chamber (1). The chancels (15) may have onepart (15 a) next to the distribution chamber that is narrow and anotherpart (15 b) that is widening into the reactor vessel. See WO 0025883. Ifthe cross-sectional area of the distribution chamber (1) is less thanthe cross-sectional area of the reactor vessel (5), the narrow parts(15′a) of the peripheral channels (15′) preferably are leaning outwardsin the gross flow direction. In this case due care should be taken toarrange for the pressure drop across each channel (15) to be essentiallythe same.

The inlet block (3) and distribution block (7) may be manufactured inmaterials, such as plastics (for instance acrylics) and stainless steel.Transparent material is particularly useful at the development stage ofa process, because it will facilitate optimization of flow velocitiesand flow directions from the conduits in a distribution chamber. Oncethe flow within the inlet device is optimised, it is often appropriateto transfer the results to an inlet device made of stainless steel orany other material that is fitted to large scale repetitive processes.The manufacture of the inlet block encompasses making holes, forinstance by drilling, for the conduits I.

The various parts of the inventive inlet device, including the reactorvessel, are hold together by techniques well-known in the field.

The Geometry of the Conduits

Each conduit has a tubular part (18,18′) and a nozzle part (19,19′). Seefor instance FIGS. 2a-f). In principle the nozzle part corresponds tothe part defining the discrete flow directions discussed above, i.e. theoutlet part of the conduit. The central axis of a conduit is the same asthe central axis of the tubular part and is typically parallel with theflow direction within the conduit (=flow direction within the tubularpart).

FIGS. 2a-c illustrate a variant of conduit Ia. In the side view (FIG.2a) and in a cross-sectional view (FIG. 2b) there is seen a centralchannel (16) for liquid flow along the length axis (17) of the tubularpart (18) of the conduit ending with a nozzle part (19) including aclosure cap. The arrow (20) shows the intended flow direction within theconduit (=within the tubular part). Below, but adjacent to, the closurecap (19) (FIGS. 2b and c), there are at least one radially directedopening (21) for radial exit of liquid from the nozzle part (19). Theangle between the direction of the openings (21) and the central axis(17) is in the interval of 90°-180°, with one or more up to all of theopenings (21) having the same direction in this respect. The preferenceis for 90°. The radial directions of the openings (21) are within aninterval of 0°-180°, such as 0°-145° or 0°-90° around the central axis(17) of the conduit (tubular part (18). The total number of openings perconduit is as said above for the number of distinct flow directions.

FIGS. 2d-f illustrate another kind of conduit. In FIGS. 2d-e there isseen a central channel (16′) for liquid flow along the length axis (17′)of the tubular part (18′) of the conduit ending with a nozzle part (19)including a closure cap. The arrow (20′) shows the intended flowdirection within the conduit (=within the tubular part). Below, butadjacent to, the closure cap (19′) (FIGS. 2b and c), there are at leastone radially directed opening (21′) for radial exit of liquid. Below,but adjacent to, the closure cap (19) (FIGS. 2b and c), there are atleast one radially directed opening (21) for radial exit of liquid fromthe nozzle part (19). The angle between the direction of an opening (21)and the central axis (17) is in the interval of 90°-180°, with one ormore up to all of the openings (21) having the same direction in thisrespect. The preference is for 90°. The radial directions (21′) cover arange which is >180° with the upper limit being 360°, such as 270°-360°and 315°-360°, around the central axis (17′) of the conduit (tubularpart, 18′). There are thus one or more openings for which there isanother opening directed in essentially the opposite direction. By“essentially opposite direction” is meant 180°±90°, such as 180°±45° or180°±10°, relative each other. The total number of openings per conduitis as said above for the flow directions.

The cross-sectional areas of openings (21,21′) and the central channel(16) will depend on the other dimensions of the inlet device, number ofconduit, the linear flow velocity in the gross flow direction etc. Anopening (21,21′) may, for instance, has a size corresponding to acircular hole of 0.5-5 mm in diameter when the inner diameter of thecentral channel (16) is within the range of 2-10 mm, with preference for4-8, mm in diameter. This is said without delineating against inventivevariants that do not utilize this specific combination of measures.

In addition to conduits Ia and Ib there may also be conduits giving riseto a flow in other directions, for instance in the same direction as theflow direction within the tubular part of a conduit, possibly at anangle up to, but less than 90°.

When positioned in the inlet block (3) the conduits I, for instance Iaand Ib, are projecting from the inlet side (11) into the distributionchamber (1). Preferably the central length axis of a conduit is in thesame direction as the gross flow direction although this does notexclude also other directions even if this might lead to arrangements ofthe openings in the conduits other than those represented by FIGS. 4a-f.This may be illustrated by placing conduits I also in a true wall ortapered parts (if present) of the distribution chamber (1) in which casethe openings in the nozzle part may have other directions than discussedpreviously. Examples are openings pointing more or less along thecentral axis (17) at an angel <90° against the flow direction in theconduit. These latter variants, when placed in a side-wall, may be usedto create a tangential or circular flow. The openings (21, 21′) areadjacent to the inlet surface (11), for instance directly at the surface(0 mm) or at a distance within 0-25, preferably 0-10 mm.

The appropriate linear flow velocity in the openings (21,21 ′) may varywidely and depends on the incoming gross liquid flow velocity, number ofconduits, number of holes in each conduits, the pressure drop over eachhole, the viscosity of the incoming liquid, the stickiness and the sizesof particulate matters in the liquid etc. In principle it is selected inthe interval of 5-1000 cm/sec, preferentially within 10-300 cm/sec.

The conduits Ia and Ib may be present in various combinations andvarious more or less regular patterns. For each type of conduits, it ispreferred to place them annularly in one or more concentric circles, forinstance with an n-numbered axis of symmetry (coinciding with thecentral axis (12)). n is an integer larger than 0, for instance 1, 2, 3,4 etc. Suitable axis of symmetry is determined by the number and/or typeof conduits etc. In case there are different kinds of conduits they maybe arranged with different type of symmetry pattern. Type Ia conduitsare typically placed annularly in an outer part of the inlet surface(11) of the distribution chamber (1) while type Ib conduits are placedmore central. In case there is only one conduit Ib, it is preferablyplaced in the centre of the surface (11) as illustrated in FIGS. 4a-e.

FIGS. 4a-e represent designs which have been tested in combination withthe distributor block illustrated in FIG. 3. The distribution chamberwas loaded with separation media leaked through the distributor and/orwas challenged with biomass in the feed-stream. The distribution blockwas attached to a squaric reactor vessel described in WO 0025883.

FIG. 4a illustrates a distribution chamber (1) with four conduits Ia(13′a,13′b,13′c,13′d; one flow direction each) which are placed in anannular pattern around a central conduit Ib (13″a, six flow directions)on the inlet surface (11) of the distribution chamber (1). The inletsurface (11) is circular. This design was challenged with biomass for 2hours at a linear flow velocity of 180 cm/hr. No biomass sedimentationcould be detected.

FIG. 4b illustrates a distribution chamber with four type Ia conduits(13′a,13′b,13′c,13′d, two flow directions per conduit) placed annularlywith one type Ib conduit in the centre (13″a, eight flow directions).This design was challenged for 5 minutes under the same flow conditionsas in FIG. 4a. Insufficient clearance of separation media from thedistribution chamber. No accumulation of biomass during extendedoperation.

FIG. 4c illustrates a distribution chamber with four type Ia conduits(13′a, 13′b, 13′c,13′d, four flow directions per conduit) placedannularly with one closed type Ib conduit in the center (13″a). Thedistribution chamber was loaded with separation media as discussed aboveand subjected to linear flow velocities of 200 cm/h and 290 cm/h in thereactor vessel. The results suggested that a higher flow velocity wasbeneficial for removing the separation media and for preventingaccumulation of biomass in the distribution chamber.

FIG. 4d illustrates a distribution chamber with four type Ia conduits(13′a,13′b,13′c,3′d, four flow directions per conduit) placed annularlywith one type Ib conduit in the centre (13″a, twelve flow directions).This design gave total separation media clearance after 40 minutes at alinear flow velocity of 200 cm/h. Biomass accumulation was avoided.

FIG. 4e illustrates the same configuration as in FIG. 4d but with theconduits Ia (14′a,14′b,14′c,14′d) closed. No total clearance ofseparation media from the distribution chamber took place at 200 cm/h.Biomass accumulation was avoided.

The inlet device of the invention can be used at linear flow velocities(in the gross flow) from 25-50 cm/h and up to about 3000 cm/h, forinstance. For particular situation the appropriate range is determinedby separation media and separation mode, sizes and number of conduitsand holes therein etc. Based on the present results that the mostimportant advantages are found within 25-1000 cm/h and in particularbelow 700 cm/h.

The separation methods discussed in the introductory part typicallycomprise a retaining step (typically an adsorption) and a subsequentrelease step (desorption or elution step). Between these two steps theremay be a washing step. Subsequent to the release step there may be aregeneration step that more or less may coincide with an equilibrationstep in case a process is made cyclic by restarting with an retainingstep. Between the release step and a regeneration step there may beinserted a cleaning step during which high salt or strongly alkalinesolutions are used. The above-mentioned main steps may consist of partsteps, which differ with respect to the buffer used. For instance arelease step may make use of one starting releasing buffer eluting onecomponent and then a subsequent different releasing buffer releasingother components.

The largest advantages with the invention are probably in the retainingstep and in the cleaning step. The reason for the advantages in theretaining step is that the inventive design will counteractsedimentation of particulate material of the feed stream in thedistribution chamber and thereby also lower the risk for stickycomponents too adhere. With respect to the cleaning step the inventivedesign will assist in removing sedimented and adhered substances fromthe distribution chamber.

Particularly great advantages is at hand in case the inventive device isused in a process in which the separation media is in form of afluidised bed, for instance with a plug flow through the bed. This meansthat the plate number should be at least 5, with preference for at least35, in this variant of the invention

The liquid containing the substance to be retained may derive from abiological fluid. The liquid may, for instance, originate from a cellculture and/or contain cell and cell debris, for instance of mammalianorigin, and/or other sticky particulates and/or sticky solutes. Howeverthis does not exclude that there also are advantages with liquidscontaining non-sticky or less sticky components, for instance intactyeast, fungi and bacterial cells, or the more sticky mixtures obtainedby breaking up these kinds of cells such as lysates, homogenates, pastesetc. The most important substances to be adsorbed in the context of theuse of the invention have polypeptide and/or carbohydrate structure.

A second aspect of the invention is a separation method as describedherein, which is characterized in the use of the inventive device at theinlet of the reactor vessel used. The preferred variants are asdescribed above. In case the conduits I are slidable and/or rotatablemounted in the inlet block, they are adjusted in regards to projectingheight and/or flow directions in order to accomplish the surface flowwith respect to the processing liquid as defined for the first aspect ofthe invention. The same objective will also be met in case the properdirections and positions for the conduits are selected from a number ofvariants in which the inlet devices has fixedly mounted conduits. It maybe advantageous to optimise the flow directions from the conduits foreach individual step of a process cycle comprising a retaining step asdefined herein.

The best mode at the priority date is the variant described in FIGS.3-4. Thus the inlet side (11) of the distribution chamber (1) has beencircular, the cross-sectional area of the reaction vessel in form of asquare, the distributor block as defined in WO 0025883 etc. Testing forappropriate conduits and flow velocities is done as outlined in the textto FIGS. 4a-e.

What is claimed is:
 1. In an inlet device for a reactor vessel (5) for aseparation method, which method includes retaining a substance on aseparation medium from a liquid passing through the reactor vessel (5)which contains the separation medium, the improvement comprisingincluding in said reactor vessel (a) a distributor block (7) forenabling a liquid flow to pass through the block into the reactor vessel(5), (b) an inlet block (3), (c) a distribution chamber (1) defined by aspace between the distributor block (7) and the outlet side (11) of theinlet block (3), (d) at least one conduit (I; 13 a,13 b . . . ) passingthrough the inlet block (3) from the inlet side (10) to the outlet side(11) of said inlet block (3) and ending in the distribution chamber (1),said at least one conduit being able to distribute liquid into thedistribution chamber (1), (e) a gross liquid flow direction goingperpendicular to the plane of the interface between the distributionblock (7) and the distribution chamber (1), and wherein one or more ofsaid at least one conduits (13 a,13 b . . . ) in the chamber (1) arecapable of moving selectively the liquid next to the inlet side surface(11) of the distribution chamber (1) along and/or against said surface(11).
 2. The inlet device according to claim 1, wherein A. one or moreconduits (Ia; 13′a,13′b . . . ) of said at least one conduit (I; 13 a,13b . . . ) are capable of directing liquid radially in one or moredistinct directions, all of which distinct directions are (i) within theinterval of 180° around the central axis of the conduit (17), (ii) inthe interval 90°-180°, relative to the liquid flow along the centralaxis (17) of the conduit, and B. said one or more conduits (Ia) aremounted in the outlet side (11) of the inlet block (3) in a manner toenable a circular liquid movement around the central axis (12) and alongthe inlet side (11) of the distribution chamber (1), and/or a liquidmovement directed towards the same side (11).
 3. The inlet device ofclaim 2, wherein said one or more conduits (Ia; 13′a,13′b . . . ) aredistributed in an even manner annularly around the central axis (12) ofthe outlet side (11) of the inlet block (3).
 4. The inlet device ofclaim 2, wherein said one or more conduits (Ib; 13″a,13″b . . . ) aredistributed in an even manner annularly around the central axis (12) ofthe outlet side (1) of the inlet block (3), with the proviso that, ifthere is only one conduit (Ib; 13″a,13″b . . . ), it is placed in thecenter of the outlet side (11) of the inlet block (3).
 5. The inletdevice of claim 2, wherein said one or more conduits (Ib; 13″a,13″b . .. ) is/are located in the inner part and said one or more conduits Ia inthe outer part of the outlet side (11) of the inlet side (3).
 6. Theinlet device of claim 2, wherein said conduits (Ia; 13′a,13′b . . . )is/are capable of directing liquid in 1-10, such as 1-5, directions, andsaid conduits Ib, if present, is/are capable of directing liquid in2-20, such as 2-15 directions.
 7. The inlet device of claim 1, whereinone or more conduits (Ib; 13″a,13″b . . . ) of said at least one conduit(I; 13 a,13 b . . . ) direct liquid flow in two or more radialdirections substantially opposite to each other.
 8. The inlet device ofclaim 7, wherein the conduits (Ib;14″a,14″b . . . ) direct flow in adirection that is in the interval of 90°-180° against the flow in theconduit flow along the length axis (17) of the conduit (14″a).
 9. Theinlet device of claim 1, wherein the distribution chamber (1) iscircular and coaxial with the central axis (12) of the reactor vessel(5), preferentially with a cross-sectional area not extending thecross-sectional area of the reactor vessel (5).
 10. The inlet device ofclaim 1, wherein said one or more conduits of said at least one conduit(I; 13 a,13 b . . . ) are rotatable and/or slidable in the inlet block(3) and/or and have and opened or closed position.
 11. The inlet deviceof claim 10, wherein the rotating, sliding and closing and/or opening ofsaid at least one conduits (I; 13 a,13 b . . . ) is externallycontrollable.